This invention relates to a method and compositions useful in controlling intraocular pressure. Specifically, this invention relates to compositions comprising tetrahydrocortisol; and methods of treatment comprising administering these compositions to treat ocular hypertension, including the glaucoma syndrome.
Tetrahydrocortisol is a normal cortisol metabolite found in urine and serum of normal humans but not in Trabecular Meshwork (TM) cells isolated from normal eyes. Cortisol is metabolized only slowly by normal TM cells. However, in TM cells from primary open angle glaucoma (POAG) patients, the rate limiting enzyme delta-4-reductase is aberrantly hyperexpressed and the activity of the 3-oxidoreductase is reduced. This enzyme imbalance leads to the accumulation of 5-alpha and 5-beta-dihydrocortisol in POAG TM cells.
While applicant is bound by no theory, it is postulated that 5-beta-dihydrocortisol is toxic to TM cells and compromises TM function. Since the trabecular meshwork is the major site for resistance to aqueous humor outflow, compromised TM function may lead to an increase in intraocular pressure. It is believed that tetrahydrocortisol may antagonize the action of 5-alpha and/or 5-beta-dihydrocortisol, in a yet to be defined manner, and that it also may function as an inhibitor of A-ring reductase activity.
Thus, it is a primary objective of the present invention to provide methods of treatment and pharmaceutical compositions which will control ocular hypertension, including retarding or delaying the progressive field of vision loss associated with glaucoma, by using tetrahydrocortisol.
Another objective of the present invention is to provide pharmaceutical compositions containing tetrahydrocortisol for topical treatment of glaucoma.
Another primary objective of the present invention is to provide pharmaceutical compositions which may be dosed topically, with the compositions being suitable for delivery in dose form in topical drops, in ophthalmic gels, and in other optically suitable dosage forms, such as ophthalmic suspensions and intracameral delivery systems.